The Northwest Himalaya is a region of rapid rock uplift and a strongly erosive climate that allows the competing influences on drainage development to be assessed in the Indus River. This study used U-Pb zircon and K-feldspar Pb isotope analysis together with conventional heavy minerals to reconstruct flood plain drainage patterns from ~20 ka. Furthermore, clay mineralogy is used to reconstruct changes in chemical weathering. U-Pb ages for zircon grains from the Indus tributaries were compared with available bedrock data in order to constrain the source of the sediment reaching the Arabian Sea. The trunk Indus is typified by <200 Ma zircons, in contrast with >800 Ma in the eastern tributaries, eroded from Himalayan sources. A significant population of grains <200 Ma in Thar Desert indicates monsoon-related eolian transport from the lower Indus. Modelling of modern delta sand that is rich in >1700 Ma zircons contrasts with modern water discharge which is dominated by the trunk Indus indicating preferential Lesser Himalayan erosion before ~7 ka. Pb isotope compositions of K-feldspars were used as an additional provenance constraint. The eastern tributaries show a clear Himalayan provenance, contrasting with radiogenic grains in the trunk Indus. Thar desert sands show isotopic values that suggest significant erosion from Karakoram, consistent with the zircon dating, as well as heavy mineral data. In turn Holocene river sands from the western edge of the desert indicate increasing reworking from the dunes prior to ~4.5 ka, linked to climatic drying. XRD clay mineralogy shows increasing smectite in the delta at 13–7.5 ka, indicating stronger chemical weathering as the summer monsoon intensified. In contrast, the upper flood plains show evidence for increased chemical weathering after ~7 ka linked to the cessation of fluvial transport under the influence of a weakening monsoon.